This proposal, which describes a 3-4 year training program, is designed to provide the candidate with the opportunity of solving an important basic research question while simultaneously acquiring the expertise needed to become a full-time independent investigator in an academic environment. The candidate received his Ph.D. in 2002 and has since been conducting research as a postdoctoral fellow at the Neurosciences Research Institute (NRI) and the Dept. of Biological Sciences at the University of Southern California (USC). The NRI consists of about 70 faculty, of whom approximately half are located in the Hedco Neuroscience Building or in close vicinity on the main USC campus. The NRI has particular strengths in computational neuroscience, systems neuroscience (learning and memory, motivational systems, vision), and cellular and molecular neuroscience where there is a strong research presence in synaptic plasticity and release mechanisms. There are many colleagues who can be of benefit to the candidate's research. The proposed mentor, Dr. Larry W. Swanson, is an acknowledged world-class authority on neuroanatomy and an expert on the neuroanatomical tract tracing techniques which form the basis of one of two major Aims of this training proposal. The proposed co-sponsor, Dr. Michel Baudry, is similarly an acknowledged authority on neurochemistry, and an expert at cellular and molecular biochemistry related to in vitro slice preparations of brain tissue, which forms the basis of the second major Aim of this training proposal. The proposed research focuses on defining the chemical phenotypes of glucosensing neurons in the brain that respond to glycemic challenges and to define the circuits between these regions and the paraventricular hypothalamus, which helps the organism respond to these challenges by initiating glucocorticoid responses. Additionally, the plan also focuses on the regulation of PVH neurons by signals that are released by these glucosensing regions. PUBLIC HEALTH RELEVANCE: Diabetics suffering from blunted counterregulatory responses to hypoglycemia may have neural impairments in sensing/responding to hypoglycemia. The proposed research aims to define what the normal brain activation pattern to hypoglycemia is, and how neurons sensing this are connected to hypothalamic structures that contribute to glucose counterregulation.